Premedication before intubation has been shown to provide pain relief, reduce the physiological effects of the procedure, and provide optimal intubating conditions. At present less than half of newborn infants intubated for mechanical ventilation or surfactant treatment in United States neonatal intensive care units (NICU) are premedicated. Premedication is used more frequently in other countries (United Kingdom 90%, France 74%), and usually includes the use of a muscle relaxant which helps to mitigate the adverse events of this procedure. The recent American Academy of Pediatrics (AAP) guideline (March 2010) which referenced five of our studies, recommended the use of premedication for all non-emergent neonatal intubations. However there are no adequately powered studies that have reported on short and longer term neonatal and neurodevelopmental outcomes of infants receiving premedication compared with those who did not. A review of our recent experience shows that the frequency of intubation attempts is associated with an increased occurrence of severe intraventricular hemorrhage and white matter injury in very preterm infants. The concept protocol within this application would capitalize on our proven leadership in trial design and completion, and would be the largest study to date to compare two premedication regimens including a single and a multiple drug approach. The study would also compare outcomes of infants non-emergently intubated in the delivery room (DR) where premedication is generally not provided, with the outcomes of non-emergently intubated infants in the NICU randomized to either drug regimen. This design would take advantage of the Network's rigorous follow-up of extremely preterm infants and would have the power to evaluate survival without neurodevelopmental impairment and prospectively compare infants that are not premedicated (DR) to those that are premedicated (NICU). The project would provide essential information for neonatologists and other care providers regarding the true benefit of premedication, and define an effective, evidence based premedication regimen for the extremely preterm infant, which would potentially improve both survival and quality of life of our most immature infants.